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Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic anion transporters.
Mycotoxin Research ( IF 3 ) Pub Date : 2020-07-11 , DOI: 10.1007/s12550-020-00399-4
Dean Karaica 1 , Vedran Micek 2 , Dubravka Rašić 3 , Maja Peraica 3 , Maja Šegvić Klarić 4 , Davorka Breljak 1
Affiliation  

Ochratoxin A (OTA) and citrinin (CIT) are mycotoxins known to co-contaminate human/animal food/feed. Their prominent nephrotoxic effects pose a threat to human and animal health. Studies have shown synergistic or additive effects of these two mycotoxins, but a clear consensus on this phenomenon does not exist. In vitro/vivo studies on OTA and CIT effects showed they elevate oxidative stress parameters. Some in vitro studies tested resveratrol (RSV) as a potential antioxidant to counteract these OTA and CIT effects. However, data on the combined effects of OTA + CIT mycotoxins and RSV on their in vivo toxicity is lacking. We used immunofluorescence microscopy and Western blotting to study the subchronic effects of individual/combined OTA (0.125 and 0.250 mg kg−1 b.w.) and CIT (20 mg kg−1 b.w.) on the localization/expression of rat renal organic anion transporters (rOats) (rOat1/Slc22a6, rOat2/Slc22a7, rOat3/Slc22a8, rOat5/Slc22a19) that mediate the secretion/reabsorption of organic anions in kidney proximal tubules. We investigated if RSV (20 mg kg−1 b.w.) can counteract the effects of both mycotoxins on the localization/expression of studied transporters. Results revealed Oat- and dose-dependent changes in protein expression of rOats. When combined with both mycotoxins, RSV decreased the protein expression of all of the studied rOats. Its effect was additive on Oat1/2/5. Thus, RSV failed to ameliorate OTA- and/or CIT-related nephrotoxic effects on the expression of studied rOats in rat kidneys.



中文翻译:

亚慢性暴露于单独的和联合的och曲霉毒素A和柠檬素会影响大鼠肾脏有机阴离子转运蛋白的表达。

ch曲毒素A(OTA)和西林蛋白(CIT)是霉菌毒素,已知会共同污染人/动物食品/饲料。它们突出的肾毒性作用对人类和动物健康构成威胁。研究表明这两种霉菌毒素具有协同作用或加和作用,但对此现象尚无明确共识。对OTA和CIT效果的体外/体内研究表明,它们提高了氧化应激参数。一些体外研究测试了白藜芦醇(RSV)作为潜在的抗氧化剂来抵消这些OTA和CIT的影响。但是,缺乏有关OTA + CIT真菌毒素和RSV对其体内毒性的联合作用的数据。我们使用免疫荧光显微镜和蛋白质印迹研究了单独/联合OTA(0.125和0.250 mg kg -1 bw)和CIT(20 mg kg -1)的亚慢性效应bw)在大鼠肾有机阴离子转运蛋白(rOats)(rOat1 / Slc22a6,rOat2 / Slc22a7,rOat3 / Slc22a8,rOat5 / Slc22a19)的定位/表达上,这些介质介导了肾脏近端小管中有机阴离子的分泌/重吸收。我们研究了RSV(20 mg kg -1 bw)是否可以抵消两种霉菌毒素对所研究转运蛋白的定位/表达的影响。结果显示rOats蛋白表达中燕麦和剂量依赖性变化。当与两种霉菌毒素结合使用时,RSV会降低所有已研究rOats的蛋白质表达。其作用是对燕麦1/2/5的累加。因此,RSV未能改善对大鼠肾脏中rOats表达的OTA和/或CIT相关的肾毒性作用。

更新日期:2020-07-13
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